EVs from cells at the early stages of chondrogenesis delivered by injectable SIS dECM promote cartilage regeneration.

Articular cartilage defect therapy is still dissatisfactory in clinic. Direct cell implantation faces challenges, such as tumorigenicity, immunogenicity, and uncontrollability. Extracellular vesicles (EVs) based cell-free therapy becomes a promising alternative approach for cartilage regeneration. Even though, EVs from different cells exhibit heterogeneous characteristics and effects. The aim of the study was to discover the functions of EVs from the cells during chondrogenesis timeline on cartilage regeneration. Here, bone marrow mesenchymal stem cells (BMSCs)-EVs, juvenile chondrocytes-EVs, and adult chondrocytes-EVs were used to represent the EVs at different differentiation stages, and fibroblast-EVs as surrounding signals were also joined to compare. Fibroblasts-EVs showed the worst effect on chondrogenesis. While juvenile chondrocyte-EVs and adult chondrocyte-EVs showed comparable effect on chondrogenic differentiation as BMSCs-EVs, BMSCs-EVs showed the best effect on cell proliferation and migration. Moreover, the amount of EVs secreted from BMSCs were much more than that from chondrocytes. An injectable decellularized extracellular matrix (dECM) hydrogel from small intestinal submucosa (SIS) was fabricated as the EVs delivery platform with natural matrix microenvironment. In a rat model, BMSCs-EVs loaded SIS hydrogel was injected into the articular cartilage defects and significantly enhanced cartilage regeneration in vivo. Furthermore, protein proteomics revealed BMSCs-EVs specifically upregulated multiple metabolic and biosynthetic processes, which might be the potential mechanism. Thus, injectable SIS hydrogel loaded with BMSCs-EVs might be a promising therapeutic way for articular cartilage defect.

Hydrophilic materials based on hydrogel polymers for enrichment of glycopeptides from serum of colorectal cancer patients.

In this work, a composite hydrogel material consisting of chitosan-based composite hydrogel was prepared by a simple and rapid synthetic method and will be named three-dimensional (3D)-IL-COF-1@CS hydrogel. Possessing a stable 3D network structure and outstanding hydrophilicity, the novel hydrogel is capable of capturing glycopeptides. The 3D-IL-COF-1@CS hydrogel showed good sensitivity (0.1 fmol/µL) and selectivity (1:2000). In addition, 19 glycopeptides were captured in standard samples. In the analysis of human serum, 148 glycopeptides assigned to 72 glycoproteins were assayed in the serum of normal individuals, and 245 glycopeptides corresponding to 100 glycoproteins were found in the serum of colorectal cancer (CRC) patients. More importantly, several functional programs based on Gene Ontology analysis supported molecular biological processes that may be relevant to the pathogenesis of CRC, including aging, fibrinogen complex, and arylesterase activity. The low cost, simplicity, rapid synthesis, and good enrichment performance have a great future in glycoproteomics analysis and related diseases.

Small Intestinal Submucosa Hydrogel Loaded With Gastrodin for the Repair of Achilles Tendinopathy.

Achilles tendinopathy (AT) is an injury caused by overuse of the Achilles tendon or sudden force on the Achilles tendon, with a considerable inflammatory infiltrate. As Achilles tendinopathy progresses, inflammation and inflammatory factors affect the remodeling of the extracellular matrix (ECM) of the tendon. Gastrodin(Gas), the main active ingredient of Astrodia has anti-inflammatory, antioxidant, and anti-apoptotic properties. The small intestinal submucosa (SIS) is a naturally decellularized extracellular matrix(dECM)material and has a high content of growth factors as well as good biocompatibility. However, the reparative effects of SIS and Gas on Achilles tendinopathy and their underlying mechanisms remain unknown. Here, it is found that SIS hydrogel loaded with gastrodin restored the mechanical strength of the Achilles tendon, facilitated ECM remodeling, and restored ordered collagen arrangement by promoting the translocation of protein synthesis. It also decreases the expression of inflammatory factors and reduces the infiltration of inflammatory cells by inhibiting the NF-κB signaling pathway. It is believed that through further research, Gas + SIS may be used in the future for the treatment of Achilles tendinopathy and other Achilles tendon injury disorders.

[Effectiveness of minimally invasive internal fixation with locking plates for mid-shaft clavicle fractures].

Objective: To explore effectiveness of minimally invasive internal fixation with locking plates for mid-shaft clavicle fractures. Methods: Between October 2022 and August 2023, 28 patients with mid-shaft clavicle fractures were treated by minimally invasive internal fixation with locking plates. There were 10 males and 18 females with a mean age of 46.2 years (range, 18-74 years). The fractures were caused by traffic accident in 16 patients, sports-related injury in 7 patients, and other injuries in 5 patients. According to Robinson classification, the fractures were classified as type 2A1 in 1 case, type 2A2 in 6 cases, type 2B1 in 15 cases, and type 2B2 in 6 cases. The interval between fracture and operation ranged from 5 hours to 21 days (median, 1.0 days). The pain visual analogue scale (VAS) score was 8.1±1.6. The VAS score at 3 days after operation and the occurrence of complications after operation were recorded. During follow-up, X-ray films were re-examined to observe the healing of the fracture; the shoulder joint function was evaluated according to the Constant-Murley score at 6 months, and the length of the incision scar (total length of the distal and proximal incisions) was measured. Results: All operations were successfully completed without any subclavian vascular or nerve damage. All incisions healed by first intention. The VAS score was 1.2±0.7 at 3 days after operation, and there was a significant difference in VAS score between pre- and post-operation ( t=8.704， P<0.001). At 1 week after operation, the patient's shoulder was basically painless, and they resumed normal life. All patients were followed up 12-20 months (mean, 13.3 months). X-ray films showed that the bone callus began to form at 2-4 months after operation (mean, 2.7 months). There was no delayed healing or non healing of the fracture, and no loosening or fracture of the internal fixators during follow-up. At 6 months after operation, the mean total incision length was 1.5 cm (range, 1.1-1.8 cm); no patient complained of numbness or paresthesia on subclavicular region or anterior chest wall. The Constant-Murley score of shoulder joint function was 93-100 (mean, 97.6). Conclusion: Minimally invasive internal fixation with locking plates is a good surgical method for treating mid-shaft clavicle fractures, with simple operation, minimal trauma, good postoperative results, and high satisfaction.

Distinguished biomimetic dECM system facilitates early detection of metastatic breast cancer cells.

Breast cancer is the most prevalent malignant tumor affecting women's health. Bone is the most common distant metastatic organ, worsening the quality of life and increasing the mortality of patients. Early detection of breast cancer bone metastasis is urgent for halting disease progression and improving tumor prognosis. Recently, extracellular matrix (ECM) with biomimetic tissue niches opened a new avenue for tumor models in vitro. Here, we developed a biomimetic decellularized ECM (dECM) system to recapitulate bone niches at different situations, bone mimetic dECM from osteoblasts (BM-ECM) and bone tumor mimetic dECM from osteosarcoma cells (OS-ECM). The two kinds of dECMs exhibited distinct morphology, protein composition, and distribution. Interestingly, highly metastatic breast cancer cells tended to adhere and migrate on BM-ECM, while lowly metastatic breast cancer cells preferred the OS-ECM niche. Epithelial-to-mesenchymal transition was a potential mechanism to initiate the breast cancer cell migration on different biomimetic dECMs. Importantly, in the nude mice model, the dECM system captured metastatic breast cancer cells as early as 10 days after orthotopic transplantation in mammary gland pads, with higher signal on BM-ECM than that on OS-ECM. Collectively, the biomimetic dECM system might be a promising tumor model to distinguish the metastatic ability of breast cancer cells in vitro and to facilitate early detection of metastatic breast cancer cells in vivo, contributing to the diagnosis of breast cancer bone metastasis.

Advances in mesenchymal stem cells therapy for tendinopathies.

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.

Assessment of the Initial Result of Screw Fixation for Proximal Crescentic Metatarsal Osteotomy with Distal Soft Tissue Reconstruction in Severe Hallux Valgus Treatment.

INTRODUCTION: Proximal crescentic metatarsal osteotomy and distal soft tissue reconstruction have been introduced to correct severe HV. The intrinsically unstable proximal first crescentic osteotomy depends on enough force fixation for stability. It is necessary to judge the number of fixation screws for osteotomy. METHOD: Fifty-two feet of 50 adult patients with severe HV were included in this study. The treatment was proximal crescentic metatarsal osteotomy with a single screw and distal soft tissue reconstruction in Group 1 and the fixation with two screws with distal soft tissue reconstruction in Group 2. Clinical and radiological follow-ups were assessed after 4 and 12 months of operation. In Group 1, HVA decreased from 46.4 ±3.28 to 19.9 ±4.70 after 12 months of operation and from 45.1 ±3.45 to 19.1 ±4.70 in Group 2. Regarding the intermetatarsal angle (IMA) in Group 1, it was changed from 18.5 ±1.98 to 9.25 ±1.11 after 12 months of operation. For group 2, it decreased from 18.3 ±1.81 to 9.53 ±1.70. Meanwhile, the AOFAS score improved from 63.1 to 83.9 after 12 months of operation in Group 1 and improved from 64.3 to 82.8 in Group 2. RESULTS: Furthermore, the VAS score reduced from 4.5±1.01 to 1.7± 0.43 in Group 1 and from 4.7±0.92 to 1.7±0.55 in Group 2 after 12 months of operation. There were no significant differences identified between Group 1 and Group 2 in terms of VAS and AOFAS scores and HVA and IMA measurements. CONCLUSION: There is less complication in two-screw fixation for crescentic osteotomy compared to a single-screw fixation.

Comparison of a minimally invasive osteosynthesis technique with conventional open surgery for transverse patellar fractures.

PURPOSE: The study aims to compare the efficacy and safety of a new minimally invasive osteosynthesis technique with those of conventional open surgery for transverse patellar fractures. METHODS: It was a retrospective study. Adult patients with closed transverse patellar fracture were included, and with open comminuted patellar fracture were excluded. These patients were divided into minimally invasive osteosynthesis technique (MIOT) group and open reduction and internal fixation (ORIF) group. Surgical time, frequency of intraoperative fluoroscopy, visual analogue scale score, flexion, extension, Lysholm knee score, infection, malreduction, implant migration and implant irritation in two groups were recorded and compared. Statistical analysis was performed by the SPSS software package (version 19). A p < 0.05 indicated statistical significance. RESULTS: A total of 55 patients with transverse patellar fractures enrolled in this study, the minimally invasive technique was performed in 27 cases, and open reduction was performed in 28 cases. The surgical time in the ORIF group was shorter than that in the MIOT group (p = 0.033). The visual analogue scale scores in the MIOT group were significantly lower than those in the ORIF group only in the first month after surgery (p = 0.015). Flexion was restored faster in the MIOT group than that in the ORIF group at one month (p = 0.001) and three months (p = 0.015). Extension was recovered faster in the MIOT group than that in the ORIF group at one month (p = 0.031) and three months (p = 0.023). The recorded Lysholm knee scores in the MIOT group were always greater than those in the ORIF group. Complications, such as infection, malreduction, implant migration, and implant irritation, occurred more frequently in the ORIF group. CONCLUSION: Compared with the ORIF group, the MIOT group reduced postoperative pain and had less complications and better exercise rehabilitation. Although it requires a long operation time, MIOT may be a wise choice for transverse patellar fractures.

Engineering the viscoelasticity of gelatin methacryloyl (GelMA) hydrogels via small "dynamic bridges" to regulate BMSC behaviors for osteochondral regeneration.

The dynamic extracellular matrix (ECM) constantly affects the behaviors of cells. To mimic the dynamics of ECM with controllable stiffness and energy dissipation, this study proposes a strategy in which a small molecule, 3,4-dihydroxybenzaldehyde (DB), was used as fast "dynamic bridges'' to construct viscoelastic gelatin methacryloyl (GelMA)-based hydrogels. The storage modulus and loss modulus of hydrogels were independently adjusted by the covalent crosslinking density and by the number of dynamic bonds. The hydrogels exhibited self-healing property, injectability, excellent adhesion and mechanical properties. Moreover, the in vitro results revealed that the viscous dissipation of hydrogels favored the spreading, proliferation, osteogenesis and chondrogenesis of bone marrow mesenchymal stem cells (BMSCs), but suppressed their adipogenesis. RNA-sequencing and immunofluorescence suggested that the viscous dissipation of hydrogels activated Yes-associated protein (YAP) by stabilizing integrin ß1, and further promoted nuclear translocation of smad2/3 and ß-catenin to enhance chondrogenesis and osteogenesis. As a result, the viscoelastic GelMA hydrogels with highest loss modulus showed best effect in cartilage and subchondral bone repair. Taken together, findings from this study reveal an effective strategy to fabricate viscoelastic hydrogels for modulating the interactions between cells and dynamic ECM to promote tissue regeneration.

Surface functionalization modification of ultra-hydrophilic magnetic spheres with mesoporous silica for specific identification of glycopeptides in serum exosomes.

Protein glycosylation of human serum exosomes can reveal significant physiological information, and the development of large-scale identification strategies is crucial for the in-depth investigation of the serum exosome glycoproteome. In this study, using surface functionalization techniques, an ultra-hydrophilic mesoporous silica magnetic nanosphere (denoted as Fe3O4-CG@mSiO2) was synthesized for the quick and accurate detection of glycopeptides from HRP digests. The Fe3O4-CG@mSiO2 nanospheres demonstrated outstanding enrichment capability, high sensitivity (5 amol/µL), good size exclusion effect (HRP digests/BSA proteins, 1:10,000), stable reusability (at least 10 times), and an excellent recovery rate (108.6 ± 5.5%). Additionally, after enrichment by Fe3O4-CG@mSiO2, 156 glycopeptides assigned to 64 proteins derived from human serum exosomes were successfully identified, which demonstrates that the nanospheres have great potential for the research of the large-scale serum exosome glycoproteome.

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment.

Osteosarcoma, with poor survival after metastasis, is considered the most common primary bone cancer in adolescents. Notwithstanding the efforts of researchers, its five-year survival rate has only shown limited improvement, suggesting that existing therapeutic strategies are insufficient to meet clinical needs. Notably, immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis. Therefore, managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease. Additionally, given the advances in nanomedicine, there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics. Here, we review the classification, characteristics, and functions of the key components of the immune microenvironment in osteosarcoma. This review also emphasizes the application, progress, and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment. Furthermore, we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy.

Single-cell RNA sequencing reveals resident progenitor and vascularization-associated cell subpopulations in rat annulus fibrosus.

Background: One of the main causes of low back pain is intervertebral disc degeneration (IDD). Annulus fibrosus (AF) is important for the integrity and functions of the intervertebral disc (IVD). However, the resident functional cell components such as progenitors and vascularization-associated cells in AF are yet to be fully identified. Purpose: Identification of functional AF cell subpopulations including resident progenitors and vascularization-associated cells. Methods: In this study, the single-cell RNA sequencing data of rat IVDs from a public database were analyzed using Seurat for cell clustering, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional analysis, StemID for stem cell identification, Monocle and RNA velocity for pseudotime differentiation trajectory validation, single-cell regulatory network inference and clustering (SCENIC) for gene regulatory network (GRN) analysis, and CellChat for cell-cell interaction analysis. Immunostaining on normal and degenerated rat IVDs, as well as human AF, was used for validations. Results: From the data analysis, seven AF cell clusters were identified, including two newly discovered functional clusters, the Grem1 + subpopulation and the Lum + â€‹subpopulation. The Grem1 + subpopulation had progenitor characteristics, while the Lum + â€‹subpopulation was associated with vascularization during IDD. The GRN analysis showed that Sox9 and Id1 were among the key regulators in the Grem1 + subpopulation, and Nr2f2 and Creb5 could be responsible for the vascularization function in the Lum + â€‹subpopulation. Cell-cell interaction analysis revealed highly regulated cellular communications between these cells, and multiple signaling networks including PDGF and MIF signaling pathways were involved in the interactions. Conclusions: Our results revealed two new functional AF cell subpopulations, with stemness and vascularization induction potential, respectively. The Translational potential of this article: These findings complement our knowledge about IVDs, especially the AF, and in return provide potential cell source and regulation targets for IDD treatment and tissue repair. The existence of the cell subpopulations was also validated in human AF, which strengthen the clinical relevance of the findings.

ATBF1 is a potential diagnostic marker of histological grade and functions via WNT5A in breast cancer.

BACKGROUND: Histological grade has been demonstrated to be an important factor of breast cancer outcome and is associated with cell differentiation and is currently being evaluated via H&E-stained sections. Molecular biomarkers are essential to improve the accuracy of histological grading. ATBF1, a large transcription factor, has been considered a tumor suppressor gene with frequent mutations or deletions in multiple cancers. In breast cancer, ATBF1 was reported to function in cell differentiation and mammary development. However, its role in the clinic has rarely been reported. METHODS: Breast cancer tissues (BCTs) and adjacent noncancerous tissues (ANCTs) were collected to analyze the expression of ATBF1 at the mRNA and protein levels. Three anti-ATBF1 antibodies recognizing independent peptides of ATBF1 (N-terminal end, middle region and C-terminal end) were applied for IHC staining. Small interfering RNA (siRNA) was used to silence ATBF1 expression and to investigate the roles of ATBF1 in MCF7 cells. Microarrays were introduced to analyze the differentially expressed genes, enriched GO terms and KEGG terms regulated by ATBF1 and its potential downstream genes, which were further confirmed in vitro and in clinical samples. RESULTS: The expression of ATBF1 was reduced in BCTs at both the mRNA and protein levels compared with that in ANCTs. ATBF1 protein was predominantly localized in the nucleus of ANCTs but in the cytoplasm of BCTs. Both the mRNA and protein levels of ATBF1 were significantly correlated with histological grade. Consistently, knockdown of ATBF1 increased stemness marker expression and reduced differentiation markers in vitro. Further analysis identified WNT5A as an essential downstream gene of ATBF1 in breast cancer cells. Treatment of WNT5A disrupted cell proliferation induced by ATBF1 silencing. In BCTs, a significant correlation was observed between the expression of WNT5A and ATBF1. CONCLUSION: The results indicated that ATBF1 expression might be a useful diagnostic marker associated with histological grade and breast cancer malignancy. WNT5A and its signaling pathway are novel mechanisms by which ATBF1 contributes to breast cancer tumorigenesis.

Enhancement of Tendon Repair Using Tendon-Derived Stem Cells in Small Intestinal Submucosa via M2 Macrophage Polarization.

(1) Background: Reconstruction of Achilles tendon defects and prevention of postoperative tendon adhesions were two serious clinical problems. In the treatment of Achilles tendon defects, decellularized matrix materials and mesenchymal stem cells (MSCs) were thought to address both problems. (2) Methods: In vitro, cell adhesion, proliferation, and tenogenic differentiation of tendon-derived stem cells (TDSCs) on small intestinal submucosa (SIS) were evaluated. RAW264.7 was induced by culture medium of TDSCs and TDSCs-SIS scaffold groups. A rat Achilles tendon defect model was used to assess effects on tendon regeneration and antiadhesion in vivo. (3) Results: SIS scaffold facilitated cell adhesion and tenogenic differentiation of TDSCs, while SIS hydrogel coating promoted proliferation of TDSCs. The expression of TGF-ß and ARG-1 in the TDSCs-SIS scaffold group were higher than that in the TDSCs group on day 3 and 7. In vivo, the tendon regeneration and antiadhesion capacity of the implanted TDSCs-SIS scaffold was significantly enhanced. The expression of CD163 was significantly highest in the TDSCs-SIS scaffold group; meanwhile, the expression of CD68 decreased more significantly in the TDSCs-SIS scaffold group than the other two groups. (4) Conclusion: This study showed that biologically prepared SIS scaffolds synergistically promote tendon regeneration with TDSCs and achieve antiadhesion through M2 polarization of macrophages.

Post-synthesis of covalent organic frameworks with dual-hydrophilic groups for specific capture of serum exosomes.

Exosomes can reflect the physiological state of parent cells and are potential disease biomarkers. In this study, we developed an innovative hydrophilic material by post-synthesis of covalent organic frameworks with dual hydrophilic groups of glutathione and cysteine (denoted as COF-S@Au@GC) to detect glycosylated exosomes in human serum. COF-S@Au@GC enriched glycosylated exosomes in human serum due to glutathione and cysteine (GC) hydrophilicity. Our results show that COF-S@Au@GC has a detection limit of 5 amol µL-1, selectivity of 1:2000, size-exclusion effect of 1:10,000, repeatability of 10 cycles, recovery of 98.3 ± 0.5%, and loading capacity of 50 mg g-1 for glycopeptides. In addition, 182 glycopeptides were detected after enrichment with COF-S@Au@GC from renal carcinoma serum, demonstrating the feasibility of enriching glycopeptides from complex biological samples. Furthermore, COF-S@Au@GC successfully captured glycosylated exosomes in the serum of renal cancer patients, with their 161 glycopeptides detected by nano liquid chromatography with tandem mass spectrometry (LC-MS/MS). This study provides a new heuristic strategy for isolating exosomes and contributes to further functional analysis of exosomes.

Multifunctional Nanofibrous Scaffolds with Angle-Ply Microstructure and Co-Delivery Capacity Promote Partial Repair and Total Replacement of Intervertebral Disc.

There is an urgent clinical need for the treatment of annulus fibrosus (AF) impairment caused by intervertebral disc (IVD) degeneration or surgical injury. Although repairing injured AF through tissue engineering is promising, the approach is limited by the complicated angle-ply microstructure, inflammatory microenvironment, poor self-repairing ability of AF cells and deficient matrix production. In this study, electrospinning technology is used to construct aligned core-shell nanofibrous scaffolds loaded with transforming growth factor-ß3 (TGFß3) and ibuprofen (IBU), respectively. The results confirm that the rapid IBU release improves the inflammatory microenvironment, while sustained TGFß3 release enhances nascent extracellular matrix (ECM) formation. Biomaterials for clinical applications must repair local AF defects during herniectomy and enable AF regeneration during disc replacement, so a box defect model and total IVD replacement model in rat tail are constructed. The dual-drug delivering electrospun scaffolds are assembled into angle-ply structure to form a highly biomimetic AF that is implanted into the box defect or used to replace the disc. In two animal models, it is found that biomimetic scaffolds with good anti-inflammatory ability enhance ECM formation and maintain the mechanical properties of IVD. Findings from this study demonstrate that the multifunctional nanofibrous scaffolds provide inspirations for IVD repair.

Fucoidan-loaded nanofibrous scaffolds promote annulus fibrosus repair by ameliorating the inflammatory and oxidative microenvironments in degenerative intervertebral discs.

Tissue engineering holds potential in the treatment of intervertebral disc degeneration (IDD). However, implantation of tissue engineered constructs may cause foreign body reaction and aggravate the inflammatory and oxidative microenvironment of the degenerative intervertebral disc (IVD). In order to ameliorate the adverse microenvironment of IDD, in this study, we prepared a biocompatible poly (ether carbonate urethane) urea (PECUU) nanofibrous scaffold loaded with fucoidan, a natural marine bioactive polysaccharide which has great anti-inflammatory and antioxidative functions. Compared with pure PECUU scaffold, the fucoidan-loaded PECUU nanofibrous scaffold (F-PECUU) decreased the gene and protein expression related to inflammation and the oxidative stress in the lipopolysaccharide (LPS) induced annulus fibrosus cells (AFCs) significantly (p<0.05). Especially, gene expression of Il 6 and Ptgs2 was decreased more than 50% in F-PECUU with 3.0 wt% fucoidan (HF-PECUU). Moreover, the gene and protein expression related to the degradation of extracellular matrix (ECM) were reduced in a fucoidan concentration-dependent manner significantly, with increased almost 3 times gene expression of Col1a1 and Acan in HF-PECUU. Further, in a 'box' defect model, HF-PECUU decreased the expression of COX-2 and deposited more ECM between scaffold layers when compared with pure PECUU. The disc height and nucleus pulposus hydration of repaired IVD reached up to 75% and 85% of those in the sham group. In addition, F-PECUU helped to maintain an integrate tissue structure with a similar compression modulus to that in sham group. Taken together, the F-PECUU nanofibrous scaffolds showed promising potential to promote AF repair in IDD treatment by ameliorating the harsh degenerative microenvironment. STATEMENT OF SIGNIFICANCE: Annulus fibrosus (AF) tissue engineering holds potential in the treatment of intervertebral disc degeneration (IDD), but is restricted by the inflammatory and oxidative microenvironment of degenerative disc. This study developed a biocompatible polyurethane scaffold (F-PECUU) loaded with fucoidan, a marine bioactive polysaccharide, for ameliorating IDD microenvironment and promoting disc regeneration. F-PECUU alleviated the inflammation and oxidative stress caused by lipopolysaccharide and prevented extracellular matrix (ECM) degradation in AF cells. In vivo, it promoted ECM deposition to maintain the height, water content and mechanical property of disc. This work has shown the potential of marine polysaccharides-containing functional scaffolds in IDD treatment by ameliorating the harsh microenvironment accompanied with disc degeneration.

Ultrasound-guided interscalene block versus intravenous analgesia and sedation for reduction of first anterior shoulder dislocation.

PURPOSE: This study aims to compare the efficacy of ultrasound-guided interscalene block (US-ISB) with that of intravenous analgesia and sedation (IVAS) in reducing first shoulder dislocation. MATERIAL AND METHODS: A prospective study was performed in 66 patients with first anterior shoulder dislocation in emergency department. The patients were divided into a US-ISB (n = 32) group and an IVAS (IVAS n = 34) group. The procedure time (anesthesia, reduction, and hospital times), pain score (before, during, and after reduction), reduction attempts, complications, and patient satisfaction were recorded and compared between the two groups. RESULTS: The anesthesia time (P < 0.01) and reduction time (P < 0.01) were shorter and the hospital time (P < 0.01) was longer in the IVAS group than in the US-ISB group. No significant differences in preoperative (P = 0.18) and postoperative (P = 0.27) pain scores were found between the two groups, but the intraoperative score of the US-ISB group was significantly higher than that of the IVAS group. More reduction attempts (P < 0.01) were recorded in the US-ISB group than that in the IVAS group. Complications (P < 0.01) such as nausea, vomiting, headache, and hypoxia occurred more frequently in the IVAS group than in the US-ISB group. No significant difference in patient satisfaction was observed between two groups (P = 0.96). CONCLUSION: Compared with IVAS group, US-ISB group reduces the time to discharge and achieves lesser complication. The pain score and reduction attempt are lower in the IVAS group than in the US-ISB group.

Exosome-based delivery nanoplatforms: next-generation theranostic platforms for breast cancer.

Breast cancer is the most frequent type of malignancy, and the leading cause of cancer-related death in women across the globe. Exosomes are naturally derived 50-150 nm nanovesicles with a variety of bioactive molecules to regulate the complex intracellular pathways involved in all stages of breast cancer development. Exosomes are also considered as a potential new generation of natural nanocarriers due to their intriguing endogenous functionalities. Recently, the development of exosome-based delivery nanoplatforms that combine the inherent unique advantages of exosomes with advanced nanotechnology has emerged as a promising area. In the present review, we first declare the fundamental principles of the relationship between exosomes and breast cancer, ranging from the initiation and progression of breast cancer, to drug resistance. More efforts are made to present a comprehensive overview of the recent advances of exosome nanotechnology for breast cancer therapy, including natural exosomes from different cell types, engineered exosomes with cargo loading and membrane modification, and artificial bionic exosomes with more stable and scalable properties. Based on the recent advanced nanotechnologies, exosome-based delivery nanoplatforms have been considered as the next-generation theranostic platforms, which sheds the light on the achievement of the clinical translation of exosomes for breast cancer therapy.

BMSCs and Osteoblast-Engineered ECM Synergetically Promotes Osteogenesis and Angiogenesis in an Ectopic Bone Formation Model.

Bone mesenchymal stem cells (BMSCs) have been extensively used in bone tissue engineering because of their potential to differentiate into multiple cells, secrete paracrine factors, and attenuate immune responses. Biomaterials are essential for the residence and activities of BMSCs after implantation in vivo. Recently, extracellular matrix (ECM) modification with a favorable regenerative microenvironment has been demonstrated to be a promising approach for cellular activities and bone regeneration. The aim of the present study was to evaluate the effects of BMSCs combined with cell-engineered ECM scaffolds on osteogenesis and angiogenesis in vivo. The ECM scaffolds were generated by osteoblasts on the small intestinal submucosa (SIS) under treatment with calcium (Ca)-enriched medium and icariin (Ic) after decellularization. In a mouse ectopic bone formation model, the SIS scaffolds were demonstrated to reduce the immune response, and lower the levels of immune cells compared with those in the sham group. Ca/Ic-ECM modification inhibited the degradation of the SIS scaffolds in vivo. The generated Ca/Ic-SIS scaffolds ectopically promoted osteogenesis according to the results of micro-CT and histological staining. Moreover, BMSCs on Ca/Ic-SIS further increased the bone volume percentage (BV/TV) and bone density. Moreover, angiogenesis was also enhanced by the Ca/Ic-SIS scaffolds, resulting in the highest levels of neovascularization according to the data ofCD31 staining. In conclusion, osteoblast-engineered ECM under directional induction is a promising strategy to modify biomaterials for osteogenesis and angiogenesis. BMSCs synergetically improve the properties of ECM constructs, which may contribute to the repair of large bone defects.